There is general concern about exposures to environmental chemicals and the impact this may have on human health, but this is of particular importance for vulnerable populations during critical periods of development. Children have unique exposure pathways and a different magnitude of exposure than adults due to differences in behaviours and physiology. Bisphenol A (BPA or 4,4’-(propane-2,2-diyl)diphenol) is a chemical intermediate in the production of polycarbonate and epoxy resins, and is used frequently in food contact materials. It has attracted significant attention due to its frequency of detection in human populations worldwide, demonstrated animal toxicity and potential adverse effects on human health. Despite a high production volume and widespread use, there is no BPA exposure data available for the Australian population, and globally, very little is known about exposures in infants and young children. The aim of this thesis is to provide the first reference range of human exposure to BPA in the Australian population, with an emphasis on children >0 – <5 years.
Biomonitoring has become the ‘gold standard’ in assessing chemical exposures because it is an aggregate measure of exposure, and can be a useful tool for risk assessment. Characterising chemical exposures in children is difficult due to challenges with recruitment, sampling techniques and limited sample volume. Pooled biological specimens can be used in biomonitoring studies to monitor levels of exposure and identify exposure trends, or to identify susceptible populations in a cost-effective manner, with little time and effort dedicated to recruitment and sample collection. Using surplus pathology specimens, two pooling strategies were employed to collect ~1400 urine samples which were stratified and pooled by age/sex and age/sex/socioeconomic status. A fully automated low-volume analytical method using online solid-phase extraction liquid chromatography tandem-mass spectrometry was developed for the analysis of total BPA (free plus conjugated species) in urine.
The geometric mean BPA concentration in children >0 – <5 years was 2.82 ng/ml for samples pooled by age/sex, and 2.57 ng/ml in children >0 – <15 years pooled by age/sex/socioeconomic status. There was a significant negative association between BPA concentration and age, but no association with sex or socioeconomic status in either population. As volume-based measures of chemical concentration in urine are influenced by individual hydration status, a urine flow model was developed to predict age-specific bodyweight-adjusted urine flow for children aged >0 to <15 years. Under steady state assumption, the model was used to estimate BPA exposure in the Australian population, and ranged from 26.2-2150 ng/kg d-1 in children (>0 to <5 years, n = 63 pools) and 20.1-165 ng/kg d-1 in an adult reference population (≥15 to <75 years, n = 28 pools). There was a significant negative association between BPA exposure and age, and exposure was significantly higher in young age groups compared with older age groups in Australia (99 and 47 ng/kg-d, respectively).
A limitation of pooled samples is the limited statistics available, so an additional study using multiple samples from children ≥2 – <4 years (n = 25, donating four samples each) was conducted to estimate variability in BPA concentrations determined from spot urine samples. The between-individual variability was approximately equal to the within-individual variability (ICC = 0.51), and a single sample resulted in correct tertile classification approximately 70% of the time, suggesting that single spot samples obtained from young children provide a reliable characterisation of absolute and relative exposure over the short time window studied.
The Australian population is exposed to BPA at levels consistent with other developed countries and beneath the current guideline values. BPA exposure is significantly higher in children, and volume-based measures of concentration may significantly underestimate true exposure if greater urine flow in children is not accounted for. BPA exposure is not associated with socioeconomic status in the Australian population, possibly due to relatively homogenous exposures in Australia, or relatively slight socioeconomic gradient in Australia compared with other developed countries. This thesis provides the first data on BPA exposures in the Australian population, and contributes to the limited number of studies on BPA exposure in children ≤5 years globally. Further, it establishes the feasibility of pooled pathology samples for identifying exposure trends in the general population, and provides previously-unknown information on short-term variability of urinary BPA in young children. This work provides a framework for future expansion to a large human biomonitoring effort in Australian children.